Naltrexone implants

There has been substantial media interest and controversy over the use of naltrexone implants for the treatment of opioid dependence. Naltrexone implants have not been approved for human use in Australia due to a lack of results from clinical trials demonstrating their pharmaceutical quality, safety and efficacy.

The National Health and Medical Research Council (NHMRC) has funded five research projects relating to naltrexone to a total of $1,507,714. A grant awarded to Professor Hulse (ID: 303106) supported a randomised controlled trial (RCT) comparing naltrexone implants with naltrexone tablets as a treatment for heroin dependence. As there is only one other published RCT on naltrexone implants (Kunøe 2009), the release of Hulse’s paper prompted an assessment of the available evidence on the safety and efficacy of naltrexone implants for opioid dependence.

Naltrexone

Naltrexone is a drug used in the management of alcohol and opioid dependence. Opioids are a class of drug that relieve pain and can create a sense of well-being. While heroin is the most well known opioid in relation to dependence, other opioids include methadone, buprenorphine, opium and the common pain-relievers morphine and codeine. When taken, naltrexone attaches to the opiate receptors in the brain and blocks them. This means that if someone tries to use any kind of opiate while they are on naltrexone, they will feel no euphoric effect from the opiate. The rationale for using naltrexone is that if a person does not experience any positive effect, they will stop using opioids.

Naltrexone is available in oral, ‘depot’ (slow-release) injection or implant preparations, however only the oral form of naltrexone has been approved for use in Australia by the Therapeutic Goods Administration. Adherence to oral medication can be difficult for some patients and depot formulations are used in other areas of medicine to overcome this. The potential benefits of an implant include less frequent dosage and reduced rates of ‘withdrawal and relapse’ between doses.

NHMRC literature review

In 2011 NHMRC reviewed current literature for the effectiveness of naltrexone implants for the treatment of opioid dependence. The review concluded that evidence is currently at an early stage and as such, naltrexone implants remain an experimental product and should only be used within a research setting. Until the relevant data are available and validated, the efficacy of the treatment, alone or in comparison to best practice, cannot be determined. NHMRC’s position on naltrexone implants is that further research on adverse effects is required before a statement on safety can be confidently made.

NHMRC does not play a role in the regulation of the clinical use of naltrexone. Relevant agencies may choose to draw on the evidence presented in the Literature Review and take action as they see appropriate.

Background to the literature review

In 2010, NHMRC staff evaluated the published scientific evidence relating to the use of Naltrexone implants due to public and professional interest in this topic. While this was not a full systematic literature review, the rigor and methodology are clearly set out in the published document.

The resulting draft literature review was considered by an expert reference group convened by NHMRC and was subjected to independent peer review. The literature review was updated to incorporate the peer review and reference group comments. In March 2011, NHMRC Council considered the literature review and recommended to the CEO that he release the review on the NHMRC website.

Membership of the Naltrexone implants reference group

Professor Fred Mendelsohn (Chair)

Director, Howard Florey Institute

Professor Jane Ingham

Chair in Palliative Medicine, University of NSW

Professor Dan Lubman

Professor of Addiction studies, Monash University

Professor Paddy Phillips

Chief Medical Officer, SA

Dr Ruth Lopert

former Principal Medical Officer, Therapeutic Goods Administration

Issues identified in review

The review identifies issues associated with naltrexone implant use and provides information on the following: